The objective of this proposed project is to determine the role of the human mononuclear phagocyte (peripheral blood monocyte) in the uptake and metabolism of plasma lipoproteins. The interaction of the cell with the individual classes and subclasses of lipoprotein will be examined with respect to binding, uptake, and degradation of the lipoproteins. Cellular interactions with normal and "abnormal" lipoproteins will be compared. Based upon the results with these native lipoproteins, lipid/lipoprotein model systems will be utilized to determine the requirements for binding and internalization by the monocyte. Monocytes from patients with 1) myeloproliferative disease and 2) xanthomas secondary to familial hyperchylomicronemia and diabetes mellitus will be compared with normal monocytes in their interaction with plasma lipoproteins. Cell extracts will be analyzed for the presence of lipolytic enzymes which may contribute to the degradation and/or remodeling of the lipid moieties of the lipoprotiens. The subcelluar localization of these enzymes will be determined to elucidate the site of hydrolysis of the lipoproteins. By studying the interaction of the normal/abnormal cell with normal/abnormal lipoproteins, we hope to define whether it is the alteration(s) in the lipoprotein or in the monocyte (or a combination of both) which is giving rise to the presence of lipid-laden tissue macrophages.